JP2017067568A - Inspection method and inspection system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an inspection method and an inspection system that can obtain an accurate inspection result associated with liquid reaction while suppressing the amount of a used liquid which does not participate in the reaction.SOLUTION: In each process of centrifugal processing, centrifugal force is made to work on an inspection chip. Firstly, in a first liquid feeding process S1, a sample liquid as a liquid participating in reaction is moved from a sample liquid introduction part to a downstream side. In a first reaction process S2, the sample liquid is held at a reaction part. In a second liquid feeding process S3, the sample liquid is moved from the reaction part to a downstream side, and a first cleaning liquid as a liquid which does not participate in the reaction is moved from a first cleaning liquid introduction part to a downstream side. In a first cleaning process S4, the first cleaning liquid is held at the reaction part. Centrifugal force in the first reaction process is larger than centrifugal force in the first cleaning process.SELECTED DRAWING: Figure 4

Description

  The present invention relates to an inspection method and an inspection system using an inspection chip in which a liquid can move.

  Conventionally, an inspection method and an inspection system using an inspection chip in which a liquid can move inside are known (for example, refer to Patent Documents 1 and 2). In Patent Document 1, the liquid stored in the analysis chip is moved to the seventh tank by centrifugal force. In the seventh tank, after the liquid reacts in a state where centrifugal force is not applied, optical measurement of the reacted liquid is performed. In the immunoassay method disclosed in Patent Document 2, the liquid in the immunoassay chip is moved to the reaction chamber by centrifugal force. By applying two or more different centrifugal forces to the immunoassay chip, measurement results of two or more test substances having different measurement ranges can be obtained.

JP 2013-50435 A JP 2008-241698 A

  Conventionally, there are cases where a liquid involved in the reaction and a liquid not involved in the reaction are used as the liquid to be moved in the inspection chip. Examples of the liquid involved in the reaction include a sample solution, a labeled antibody solution, and a substrate solution. Examples of the liquid not involved in the reaction include a cleaning liquid. When inspecting a liquid reaction using an inspection chip, for example, in order to suppress the size and inspection cost of the inspection chip, it is preferable that the amount of liquid not involved in the reaction is small. However, if the amount of liquid that is not involved in the reaction is suppressed, there is a possibility that an accurate test result regarding the liquid reaction cannot be obtained.

  An object of the present invention is to provide an inspection method and an inspection system capable of obtaining an accurate inspection result relating to a liquid reaction while suppressing the amount of liquid that is not involved in the reaction.

  A first aspect of the present invention is an inspection method for performing an inspection by applying acceleration to an inspection chip, wherein the inspection chip is a first liquid that is a liquid involved in a reaction and a liquid that is not involved in a reaction. An introduction part that is an area into which two liquids are introduced; a holding part that is connected to a downstream side of the introduction part and that can hold the first liquid and the second liquid that have flowed out of the introduction part; The inspection method includes: a first movement step for moving the first liquid downstream from the introduction unit by applying acceleration to the inspection chip; and after the execution of the first movement step, the inspection A first holding step in which the first liquid is held in the holding portion by applying acceleration to the chip, and an acceleration is applied to the inspection chip after execution of the first holding step. Is moved downstream from the holding portion, and the front After the second moving step for moving the second liquid downstream from the introducing portion and the second moving step, the holding portion holds the second liquid by applying acceleration to the inspection chip. A second holding step, wherein an acceleration applied to the inspection chip in the first holding step is greater than an acceleration applied to the inspection chip in the second holding step.

  According to this, the liquid is operated as follows by applying acceleration to the inspection chip in each step of the inspection method. First, in the first movement step, the first liquid, which is a liquid involved in the reaction, is moved downstream from the introduction part. Next, in the first holding step, the first liquid is held in the holding unit. Next, in the second movement step, the first liquid is moved downstream from the holding part, and the second liquid that is a liquid not involved in the reaction is moved downstream from the introduction part. Next, in the second holding step, the second liquid is held in the holding unit. The acceleration in the first holding process is larger than the acceleration in the second holding process. Since the acceleration in the first holding step is larger than the acceleration in the second holding step, the surface tension between the first liquid held in the first holding step and the holding portion and the second tension held in the second holding step. In the surface tension between the liquid and the holding part, a force in a direction in which the surface tension between the first liquid and the holding part is canceled by the acceleration tends to work. That is, when the liquid amounts of the first liquid and the second liquid are equal, the contact area between the second liquid and the holding part in the second holding process is the contact between the first liquid and the holding part in the first holding process. Greater than area. Even when the liquid volume of the second liquid is smaller than the liquid volume of the first liquid, the second liquid can contact the entire region of the holding portion that is in contact with the first liquid. Therefore, an accurate test result relating to the liquid reaction can be obtained while suppressing the amount of liquid that is not involved in the reaction.

  The holding part includes a reaction part in which a solid-phased antibody is disposed, the first liquid is a liquid that reacts with the solid-phased antibody in the reaction part, and the second liquid is a liquid that reacts with the reaction part. The first holding step causes the first liquid to react with the immobilized antibody by holding the first liquid in the reaction part, and the second holding step includes the first holding step. You may wash | clean the said reaction part with said 2nd liquid by hold | maintaining two liquids in the said reaction part. In this case, in the first holding step, the first liquid is reacted with the immobilized antibody disposed in the reaction part. In the second holding step, the reaction part is washed with the second liquid. Thereby, in the process after a 2nd holding process, the liquid can be made to react correctly at the process part, suppressing the usage-amount of the washing | cleaning liquid which does not participate in reaction.

  The first solution includes a sample solution containing a substance to be examined, a labeled antibody solution containing an enzyme-labeled antibody, and a substrate solution that undergoes an enzyme reaction with the enzyme-labeled antibody, and the second solution is a first washing solution as the washing solution. And the second cleaning solution, wherein the first moving step moves the sample solution from the introduction unit to the downstream side, and the first holding step holds the sample solution in the reaction unit, thereby The target substance is bound to the solid-phased antibody to generate a first conjugate, the second moving step moves the first washing liquid downstream from the introduction part, and the second holding step includes By holding the first cleaning liquid in the reaction part, components other than the first conjugate remaining in the reaction part are removed, and the inspection method further includes the inspection chip after execution of the second holding step. By applying acceleration to the first cleaning liquid, By moving the reaction from the reaction unit to the downstream side and moving the labeled antibody solution from the introduction unit to the downstream side, and performing the third movement step, by applying acceleration to the test chip, Execution of the third holding step, in which the labeled antibody solution is held in the reaction section and the enzyme-labeled antibody is specifically bound to the first conjugate to generate a second conjugate, and the third holding step Thereafter, by applying acceleration to the test chip, a fourth moving step of moving the labeled antibody solution from the reaction unit to the downstream side and moving the second cleaning solution from the introduction unit to the downstream side; and After executing the fourth moving step, by applying acceleration to the inspection chip, the second cleaning liquid is retained in the reaction unit, and components other than the second conjugate remaining in the reaction unit are removed. A fourth holding step and the fourth holding step. A fifth moving step of moving the second cleaning liquid from the reaction unit to the downstream side and moving the substrate solution from the introduction unit to the downstream side by applying acceleration to the inspection chip after the step is performed; A fifth holding step of causing the reaction unit to hold the substrate solution by reacting the substrate solution with the second conjugate by applying acceleration to the test chip after execution of the fifth moving step; The acceleration applied to the inspection chip in each of the first holding step, the third holding step, and the fifth holding step is the second holding step and the fourth holding step, respectively. It may be greater than the acceleration applied to the inspection chip.

  In this case, in the first holding step, the sample solution is held in the reaction unit, and a first conjugate in which the test target substance and the immobilized antibody are bound is generated. In the second holding step, the first cleaning liquid is held in the reaction part, and components other than the first conjugate remaining in the reaction part are removed. Next, in the third movement step, the first cleaning solution is moved downstream from the reaction unit, and the labeled antibody solution is moved downstream from the introduction unit. Next, in the third holding step, the labeled antibody solution is held in the reaction part to generate a second conjugate in which the enzyme-labeled antibody and the first conjugate are specifically bound. Next, in the fourth movement step, the labeled antibody solution is moved downstream from the reaction unit, and the second cleaning solution is moved downstream from the introduction unit. Next, in the fourth holding step, the second cleaning liquid is held in the reaction part, and components other than the second conjugate remaining in the reaction part are removed. Next, in the fifth movement step, the second cleaning liquid is moved downstream from the reaction part, and the substrate solution is moved downstream from the introduction part. Next, in the fifth holding step, the substrate solution is held in the reaction part, and the substrate solution is reacted with the second conjugate. Each acceleration in the first, third, and fifth holding steps is greater than each acceleration in the second and fourth holding steps.

  That is, the acceleration of each process in which the first liquid is reacted in the reaction part is larger than the acceleration of each process in which the reaction part is washed with the second liquid. Thereby, the surface tension between the first liquid and the reaction part in each of the first, third, and fifth holding processes, and the second liquid and the reaction part in each of the second and fourth holding processes. In this surface tension, a force in a direction in which the surface tension between the first liquid and the reaction portion is offset by the acceleration tends to work. That is, when the liquid amounts of the first liquid and the second liquid are equal, the contact area between the first liquid and the reaction part in each of the first, third, and fifth holding steps is the second and fourth. It is larger than the contact area between the second liquid and the reaction part in each of the holding steps. Even when the amount of the first cleaning liquid is less than that of the sample liquid, the first cleaning liquid can contact the entire region of the reaction part that has contacted the sample liquid, so that components other than the first conjugate remaining in the reaction part can be reliably ensured. Can be removed. Even when the second washing solution is less than the labeled antibody solution, the second washing solution can contact the entire region of the reaction portion that has contacted the labeled antibody solution, so that components other than the second conjugate remaining in the reaction portion Can be reliably removed. Therefore, a more accurate reaction result is obtained when the substrate solution is reacted with the second conjugate in the fifth holding step.

  The acceleration applied to the inspection chip in each of the first holding step, the third holding step, and the fifth holding step is the same as that of the first moving step, the third moving step, and the fifth moving step. The acceleration applied to the inspection chip in each case may be equal to or lower than the acceleration. In this case, the acceleration of each process for reacting the first liquid in the reaction unit is equal to or less than the acceleration of each process for moving the liquid in the inspection chip. Thereby, the energy consumption accompanying execution of a test | inspection method can be suppressed, and a liquid can be moved correctly within a test | inspection chip.

  The acceleration applied to the inspection chip in the first holding step may be greater than or equal to the acceleration applied to the inspection chip in each of the third holding step and the fifth holding step. Since the first holding step is executed first among the first, third, and fifth holding steps, the amount of the first conjugate produced has a great influence on the final inspection result. Therefore, the liquid level position of the sample liquid in the reaction part can be accurately controlled by making the acceleration of the first holding process equal to or higher than the accelerations of the third and fifth holding processes. Thereby, the contact area between the sample liquid and the reaction part is accurately controlled, and the amount of the first conjugate produced is accurately controlled, so that an accurate test result regarding the liquid reaction can be obtained.

  The acceleration applied to the inspection chip in the second holding step may be greater than the acceleration applied to the inspection chip in the fourth holding step. In this case, since the acceleration of the second holding step is larger than the acceleration of the fourth holding step, the surface tension between the first cleaning liquid and the reaction part held in the second holding step and the fourth holding step are held. In the surface tension between the second cleaning liquid and the reaction part, the force in the direction in which the surface tension between the first cleaning liquid and the reaction part is offset by the acceleration tends to work. That is, when the liquid amounts of the first cleaning liquid and the second cleaning liquid are equivalent, the contact area between the first cleaning liquid and the reaction part in the second holding process is the contact between the second cleaning liquid and the reaction part in the fourth holding process. Greater than area. Even when the amount of the second cleaning liquid is smaller than the amount of the first cleaning liquid, the second cleaning liquid can contact the entire region of the reaction portion that is in contact with the first cleaning liquid. Therefore, since the wide range of the reaction part can be cleaned while suppressing the amount of the second cleaning liquid not involved in the reaction, an accurate test result regarding the liquid reaction can be obtained.

  The fourth moving step includes a plurality of cleaning liquid moving steps for dividing the second cleaning liquid into a plurality of times and moving the second cleaning liquid to the downstream side from the introduction unit, and the fourth holding step is performed by each of the plurality of cleaning liquid moving steps. A plurality of washing liquid holding steps for holding the second washing liquid moved downstream from the introduction part in the reaction part after the labeled antibody liquid has been moved downstream each time it is executed, The plurality of cleaning liquid discharge processes include an initial cleaning process that is first executed among the plurality of cleaning liquid discharging processes, and at least one subsequent cleaning process that is executed after the initial cleaning process, The acceleration applied to the inspection chip in each of the subsequent cleaning steps may be greater than or equal to the acceleration applied to the inspection chip in the initial cleaning step.

  In this case, in the fourth moving step, the second cleaning liquid is moved to the downstream side from the introduction portion in a plurality of times. The fourth holding process includes a plurality of cleaning liquid holding processes that are executed each time the second cleaning liquid is moved downstream from the introduction unit. In each of the plurality of washing liquid holding steps, the second washing liquid moved downstream from the introduction part is held in the reaction part after the labeled antibody liquid has been moved downstream. The plurality of cleaning liquid holding processes include an initial cleaning process executed first and a subsequent cleaning process executed thereafter. The acceleration of the subsequent cleaning process is greater than or equal to the acceleration of the initial cleaning process. Therefore, removal of components other than the second conjugate remaining in the reaction part is performed in a plurality of times by a plurality of washing liquid holding steps. Since the acceleration of the initial cleaning process is the largest among the plurality of cleaning liquid holding processes, the second cleaning liquid can clean the wide range of the reaction part in the initial cleaning process.

  Each of the first liquid and the second liquid may have a contact angle of 90 degrees or less with respect to the wall surface of the holding portion. In this case, even when the liquid volume of the second liquid is smaller than the liquid volume of the first liquid, the second liquid can contact the entire region of the holding portion that is in contact with the first liquid. Therefore, an accurate test result relating to the liquid reaction can be obtained while suppressing the amount of the second liquid that is not involved in the reaction.

  The acceleration applied to the inspection chip may be a centrifugal force. In this case, the above-described inspection method can be realized by applying centrifugal force to the inspection chip and adjusting the direction in which the centrifugal force acts.

  A second aspect of the present invention is an inspection system including an inspection chip in which a liquid can move and an inspection device that applies acceleration to the inspection chip, the inspection chip being a liquid involved in a reaction. An introduction part that is a region into which the first liquid and a second liquid that is not involved in the reaction are introduced; the first liquid that is connected to the downstream side of the introduction part and flows out of the introduction part; A first moving step of moving the first liquid from the introduction section to the downstream side by applying acceleration to the inspection chip. First holding means for executing the first holding step for holding the first liquid in the holding portion by applying acceleration to the inspection chip after the first moving step is executed. Means and after execution of the first holding step A second moving step is performed in which an acceleration is applied to the inspection chip to move the first liquid from the holding part to the downstream side and to move the second liquid from the introduction part to the downstream side. And a second holding unit that executes a second holding step of holding the second liquid in the holding unit by applying an acceleration to the inspection chip after the second moving step. The acceleration applied to the inspection chip in the first holding step is larger than the acceleration applied to the inspection chip in the second holding step. According to this, there exists an effect | action similar to a 1st aspect.

It is a figure which shows the structure of the test | inspection system 3 containing the test | inspection apparatus 1 and the control apparatus 90. FIG. It is a front view of the test | inspection chip 2. FIG. It is an enlarged front view of the waste liquid part 700 vicinity. It is a flowchart of a centrifugation process. It is a state transition diagram of the test | inspection chip 2 in a centrifugation process. FIG. 6 is a state transition diagram continuing from FIG. 5. FIG. 7 is a state transition diagram continuing from FIG. 6. It is sectional drawing to which the reaction part 380 was expanded.

  DESCRIPTION OF EMBODIMENTS Embodiments embodying the present invention will be described with reference to the drawings. FIG. 1 shows a plane of the inspection apparatus 1 constituting the inspection system 3 and functional blocks inside the control apparatus 90.

<1. Schematic structure of inspection system 3>
A schematic structure of the inspection system 3 will be described with reference to FIG. The inspection system 3 of the present embodiment includes an inspection chip 2 that can store a sample and a reagent that are liquids, and an inspection apparatus 1 that performs an inspection using the inspection chip 2. When the inspection device 1 rotates the inspection chip 2 around the vertical axis A <b> 1 separated from the inspection chip 2, centrifugal force acts on the inspection chip 2. When the inspection device 1 rotates the inspection chip 2 around the horizontal axis A2, the direction of the centrifugal force acting on the inspection chip 2 as viewed from the inspection chip 2 is switched. In addition, since the inspection system 3 and the inspection apparatus 1 according to the present embodiment have a well-known structure as described in Japanese Patent Application Laid-Open No. 2012-78107, the schematic structure of the inspection apparatus 1 will be described below. .

<2. Structure of the inspection apparatus 1>
The structure of the inspection apparatus 1 will be described with reference to FIG. In the following description, the upper side, the lower side, the right side, the left side, the front side of the paper surface, and the rear side of the paper surface in FIG. . In the present embodiment, the direction of the vertical axis A1 is the vertical direction of the inspection apparatus 1, and the direction of the horizontal axis A2 is the direction of the speed when the inspection chip 2 is rotated about the vertical axis A1. FIG. 1 shows a state in which the top plate of the upper housing 30 of the inspection apparatus 1 has been removed.

  As shown in FIG. 1, the inspection apparatus 1 includes an upper housing 30, a lower housing 31, an upper plate 32, a turntable 33, an angle changing mechanism 34, and a control device 90. The turntable 33 is a disk rotatably provided on the upper side of an upper plate 32 described later. The inspection chip 2 is held above the turntable 33. The angle changing mechanism 34 is a drive mechanism provided on the turntable 33. The angle changing mechanism 34 rotates each of the inspection chips 2 around the horizontal axis A2. The upper housing 30 is fixed to an upper plate 32 described later, and a measurement unit 7 that performs optical measurement on the inspection chip 2 is provided inside. The control device 90 is a controller that controls various processes of the inspection device 1.

  A schematic structure of the lower housing 31 will be described. The lower housing 31 has a box-shaped frame structure in which frame members are combined. An upper plate 32 that is a rectangular plate material is provided on the upper surface of the lower housing 31. A drive mechanism that rotates the turntable 33 around the vertical axis A1 is provided in the lower housing 31 as follows.

  A spindle motor 35 that supplies a driving force for rotating the turntable 33 is installed on the left side in the lower housing 31. A shaft 36 of the main shaft motor 35 protrudes upward, and a pulley 37 is fixed. A vertical main shaft 57 extending upward from the inside of the lower housing 31 is provided at the center of the lower housing 31. The main shaft 57 passes through the upper plate 32 and protrudes above the lower housing 31. The upper end portion of the main shaft 57 is connected to the center portion of the turntable 33.

  The main shaft 57 is rotatably held by a support member (not shown) provided immediately below the upper plate 32. A pulley 38 is fixed to the main shaft 57 below the support member. A belt 39 is stretched over the pulley 37 and the pulley 38. When the main shaft motor 35 rotates the shaft 36, the driving force is transmitted to the main shaft 57 via the pulley 37, the belt 39, and the pulley 38. At this time, the turntable 33 rotates around the main shaft 57 in conjunction with the rotation of the main shaft 57.

  A guide rail (not shown) extending in the vertical direction inside the lower housing 31 is provided on the right side in the lower housing 31. A T-shaped plate (not shown) is movable in the vertical direction in the lower housing 31 along the guide rail.

  The aforementioned main shaft 57 is a cylindrical body having a hollow inside. An inner shaft (not shown) is a shaft that can move in the vertical direction inside the main shaft 57. The upper end portion of the inner shaft passes through the main shaft 57 and is connected to the rack gear 43. A bearing (not shown) is provided at the left end of the T-shaped plate. Inside the bearing, the lower end portion of the inner shaft is rotatably held.

  A stepping motor 51 for moving the T-shaped plate up and down is fixed in front of the T-shaped plate. The shaft 58 of the stepping motor 51 protrudes rearward, that is, downward in FIG. A disc-shaped cam plate (not shown) is fixed to the tip of the shaft 58. A cylindrical projection (not shown) is provided on the rear surface of the cam plate. The tip of the protrusion is inserted into a groove (not shown). The protrusion can slide in the groove. When the stepping motor 51 rotates the shaft 58, the protrusion moves up and down in conjunction with the rotation of the cam plate. At this time, the T-shaped plate moves up and down along the guide rail in conjunction with the protrusion inserted in the groove.

  The detailed structure of the angle changing mechanism 34 will be described. The angle changing mechanism 34 has a pair of L-shaped plates 60 fixed to the upper surface of the turntable 33. Each L-shaped plate 60 extends upward from a base portion fixed in the vicinity of the center of the turntable 33, and its upper end portion extends outward in the radial direction of the turntable 33. A rack gear 43 (not shown) fixed to the inner shaft is provided between the pair of L-shaped plates 60. The rack gear 43 is a metal plate-like member that is long in the vertical direction, and gears are respectively carved on both end faces.

  On the front end side in the extending direction of each L-shaped plate 60, a horizontal support shaft 46 having a gear 45 is rotatably supported. The support shaft 46 is fixed to the inspection chip 2 via a mounting holder (not shown). For this reason, the inspection chip 2 also rotates around the support shaft 46 in conjunction with the rotation of the gear 45. Between the gear 45 and the rack gear 43, a pinion gear 44 supported by an L-shaped plate 60 so as to be rotatable about a horizontal axis (not shown) is interposed. The pinion gear 44 meshes with the gear 45 and the rack gear 43, respectively. In conjunction with the vertical movement of the rack gear 43, the pinion gear 44 and the gear 45 are driven to rotate, and the inspection chip 2 is rotated about the support shaft 46.

  In the present embodiment, as the main shaft motor 35 rotationally drives the turntable 33, the inspection chip 2 rotates around the main shaft 57 that is a vertical axis, and a centrifugal force acts on the inspection chip 2. The rotation around the vertical axis A1 of the inspection chip 2 is referred to as revolution. On the other hand, as the stepping motor 51 moves the inner shaft up and down, the inspection chip 2 rotates about the support shaft 46 which is a horizontal axis, and the direction of the centrifugal force acting on the inspection chip 2 changes relatively. The rotation around the horizontal axis A2 of the inspection chip 2 is called autorotation.

  In a state where the T-shaped plate is lowered to the lowermost end of the movable range, the rack gear 43 is also lowered to the lowermost end of the movable range. At this time, the inspection chip 2 is in a steady state where the rotation angle is 0 degree. Further, in the state where the T-shaped plate is raised to the uppermost end of the movable range, the rack gear 43 is also raised to the uppermost end of the movable range. At this time, the test | inspection chip 2 will be in the state rotated 180 degree | times centering on the horizontal axis line A2 from the steady state. That is, the angle width that the inspection chip 2 can rotate is the rotation angle of 0 to 180 degrees. In the present embodiment, the rotation angle is controlled with an angle width of 0 degree to 90 degrees in a centrifugal process (see FIG. 4) described later.

  The detailed structure of the upper housing 30 will be described. As shown in FIG. 1, the upper housing 30 has a box-like frame structure in which frame members are combined, and is installed on the upper left side of the upper plate 32. More specifically, the upper housing 30 is provided outside the range in which the inspection chip 2 is rotated as viewed from the main shaft 57 at the rotation center of the turntable 33.

  The measurement unit 7 provided inside the upper housing 30 includes a light source 71 that emits measurement light, and an optical sensor 72 that detects the measurement light emitted from the light source 71. The light source 71 and the optical sensor 72 are disposed on both the front and rear sides of the turntable 33 outside the rotation range of the inspection chip 2. In the present embodiment, the position on the left side of the main shaft 57 in the reciprocable range of the inspection chip 2 is the measurement position at which the inspection chip 2 is irradiated with the measurement light. When the inspection chip 2 is at the measurement position, the measurement light connecting the light source 71 and the optical sensor 72 intersects the front surface and the rear surface of the inspection chip 2 substantially perpendicularly.

<3. Electrical configuration of control device 90>
The electrical configuration of the control device 90 will be described with reference to FIG. The control device 90 includes a CPU 101 that controls the main control of the inspection device 1, a RAM 102 that temporarily stores various data, and a ROM 103 that stores a control program. Connected to the CPU 101 are an operation unit 104 for a user to input an instruction to the control device 90, a hard disk device 105 for storing various data and programs, and a display 106 for displaying various information. As the control device 90, a personal computer may be used, or a dedicated control device may be used.

  Further, a revolution controller 97, a rotation controller 98, and a measurement controller 99 are connected to the CPU 101. The revolution controller 97 controls the revolution of the inspection chip 2 by transmitting a control signal for rotating the spindle motor 35 to the spindle motor 35. The rotation controller 98 controls the rotation of the inspection chip 2 by transmitting a control signal for rotating the stepping motor 51 to the stepping motor 51. The measurement controller 99 performs the optical measurement of the inspection chip 2 by driving the measurement unit 7. Specifically, the measurement controller 99 transmits a control signal for executing light emission of the light source 71 and light detection of the optical sensor 72 to the light source 71 and the optical sensor 72. The CPU 101 controls the revolution controller 97, the rotation controller 98, and the measurement controller 99.

<4. Overall Structure of Inspection Chip 2>
With reference to FIG. 2, the whole structure of the test | inspection chip 2 based on this embodiment is demonstrated. In the following description, the upper, lower, left, right, front side, and back side of FIG. 2 are the upper, lower, left, right, front, and rear sides of the inspection chip 2, respectively. . In the present embodiment, the inspection chip 2 is used, and the inspection is performed by the ELISA method.

  As shown in FIG. 2, the inspection chip 2 has a square shape having an upper side portion 81, a lower side portion 84, a right side portion 82, and a left side portion 83 when viewed from the front as an example, and is a transparent composite having a predetermined thickness. Resin plate 19 is mainly used. The front surface 203 of the plate 19 is sealed with a sheet 291 made of a transparent synthetic resin thin plate. Between the plate material 19 and the sheet 291, a liquid flow path 25 is formed through which the liquid sealed in the inspection chip 2 can flow. The liquid channel 25 is a recess formed at a predetermined depth on the front surface 203 and extends in a direction orthogonal to the front-rear direction, which is the thickness direction of the plate material 19. The sheet 291 seals the flow path forming surface of the plate material 19. The sheet 291 is not shown except in FIG.

  The liquid flow path 25 includes a sample solution introduction unit 310, a first washing solution introduction unit 320, a labeled antibody solution introduction unit 330, a second washing solution introduction unit 340, a substrate solution introduction unit 350, a stop solution introduction unit 360, a common receiving unit 370, Reaction unit 380, measurement unit 390, waste liquid unit 700, first receiving unit 450, second receiving unit 460, third receiving unit 470, fourth receiving unit 550, injection path 480, 490.500, 510, 520, 530, etc. including. The sample solution introduction unit 310, the first washing solution introduction unit 320, the labeled antibody solution introduction unit 330, the second washing solution introduction unit 340, the substrate solution introduction unit 350, the stop solution introduction unit 360, the reaction unit 380, and the measurement unit 390, respectively. It is recessed downward and opens upward.

  A solid phased antibody, which is a solid phased antibody, is disposed on the wall surface forming the reaction part 380. The sample solution introduction unit 310, the first washing solution introduction unit 320, the labeled antibody solution introduction unit 330, the second washing solution introduction unit 340, the substrate solution introduction unit 350, and the stop solution introduction unit 360 are the sample solution 91 and the first washing solution, respectively. 92, a site where the labeled antibody solution 93, the second washing solution 94, the substrate solution 95, and the stop solution 96 are held.

  The sample liquid 91 is, for example, a liquid containing components of a test target substance such as blood, plasma, blood cells, bone marrow, urine, vaginal tissue, epithelial tissue, tumor, semen, saliva, animal tissue, animal blood, or foodstuffs. It is. The substance to be examined contained in the sample solution 91 is combined with the immobilized antibody. The first washing liquid 92 is a liquid for removing components of the sample liquid 91 that are not bound to the immobilized antibody. The labeled antibody solution 93 is a liquid containing an enzyme labeled antibody. An enzyme-labeled antibody is an antibody labeled with an enzyme. The enzyme-labeled antibody contained in the labeled antibody solution 93 is specifically bound to the test substance and the conjugate of the immobilized antibody.

  The second washing liquid 94 is a liquid for removing the components of the labeled antibody liquid 93 that are not bound to the conjugate of the substance to be examined and the immobilized antibody. The substrate solution 95 is a liquid that is brought into contact with the solid-phased antibody after being washed with the second washing liquid 94 and is enzymatically reacted with the enzyme-labeled antibody. The stop solution 96 is a liquid that is mixed with the substrate solution 95 to stop the progress of the enzyme reaction. In the present embodiment, in the optical measurement described later, a fluorescent substance or a colored substance generated by the enzyme reaction of the substrate solution 95 is detected, and the inspection target substance is measured.

  In the present embodiment, each of the sample liquid 91, the first cleaning liquid 92, the labeled antibody liquid 93, the second cleaning liquid 94, the substrate solution 95, and the stop liquid 96 and the wall surface forming the liquid flow path 25 are in static contact with each other. The contact angle, which is the angle formed in this case, is 90 degrees or less. Hereinafter, in order to facilitate understanding, the contact angles of the sample liquid 91, the first cleaning liquid 92, the labeled antibody liquid 93, the second cleaning liquid 94, the substrate solution 95, and the stop liquid 96 are the same as each other. To do.

  The sample liquid introduction part 310 is provided in the upper right part of the inspection chip 2. The injection path 480 extends upward from the upper left part of the sample solution introduction part 310 and penetrates the upper side part 81. The injection path 480 is a part where the sample liquid 91 is injected into the sample liquid introduction unit 310. The first cleaning liquid introduction unit 320 is positioned below the sample liquid introduction unit 310. The injection path 490 extends upward from the upper left part of the first cleaning liquid introduction part 320 and penetrates the upper side part 81. The injection path 490 is a part for injecting the first cleaning liquid 92 into the first cleaning liquid introduction part 320. A common receiving part 370 is provided on the lower right side of the first cleaning liquid introducing part 320. The common receiving part 370 is a recessed part opened upward. The upper right part of the sample liquid introduction part 310 and the upper right part of the first cleaning liquid introduction part 320 are connected to the common receiving part 370 via a flow path 610 extending downward.

  The stop liquid introducing part 360 is provided in the upper left part of the inspection chip 2. The injection path 530 extends upward from the upper left portion of the stop liquid introducing portion 360 and penetrates the upper side portion 81. The injection path 530 is a part for injecting the stop liquid 96 into the stop liquid introducing part 360. The substrate solution introduction unit 350 is located below the stop solution introduction unit 360. The injection path 520 extends upward from the upper left part of the substrate solution introduction part 350 and penetrates the upper side part 81. The injection path 520 is a part for injecting the substrate solution 95 into the substrate solution introduction part 350.

  The second cleaning liquid introduction unit 340 is located below the substrate solution introduction unit 350. The injection path 510 extends upward from the upper left part of the second cleaning liquid introduction part 340 and penetrates the upper side part 81. The injection path 510 is a part for injecting the second cleaning liquid 94 into the second cleaning liquid introduction part 340. The labeled antibody solution introduction unit 330 is located below the substrate solution introduction unit 350. The injection path 500 extends upward from the upper left part of the labeled antibody solution introduction part 330 and penetrates the upper side part 81. The injection path 500 is a part for injecting the labeled antibody solution 93 into the labeled antibody solution introduction unit 330.

  The wall surface downstream of the wall surfaces forming the sample liquid introduction part 310 is referred to as a first wall surface 501. The downstream wall surface among the wall surfaces forming the first cleaning liquid introducing section 320 is referred to as a second wall surface 502. The downstream wall surface among the wall surfaces forming the labeled antibody solution introducing portion 330 is referred to as a third wall surface 503. The downstream wall surface among the wall surfaces forming the stop liquid introducing portion 360 is referred to as a fourth wall surface 504. The downstream wall surface among the wall surfaces forming the substrate solution introducing portion 350 is referred to as a fifth wall surface 505. The downstream wall surface among the wall surfaces forming the second cleaning liquid introducing portion 340 is referred to as a sixth wall surface 506.

The inclination angles of the first to sixth wall surfaces 501 to 506 are R1, R2, R3, R4, R5, and R6, respectively. In FIG. 2, as an example, the inclination angles R <b> 1 to R <b> 6 are shown by angles formed by the first to sixth wall surfaces 501 to 506 and the downward direction. The inclination angles R1 to R6 have the relationship of the following formula (1).
R3, R4, R5, R6>R2> R1 (1)
In addition, although R3-R6 are mutually the same angle in this embodiment, they may be mutually different angles.

  The first receiving part 450 is a flow path that extends downward from the upper right part of the stop liquid introducing part 360. The first receiving portion 450 is recessed to the right. The lower left part of the first receiving part 450 is connected to the substrate solution introducing part 350. The second receiving part 460 is a flow path extending downward from the upper right part of the substrate solution introducing part 350. The second receiving part 460 is recessed rightward. The lower left part of the second receiving part 460 is connected to the second cleaning liquid introducing part 340. The third receiving part 470 is a flow path extending downward from the upper right part of the second cleaning liquid introducing part 340. The third receiving part 470 is recessed rightward. The lower left part of the third receiving part 470 is connected to the labeled antibody solution introducing part 330.

  The right part of the labeled antibody solution introducing unit 330 extends obliquely upward to the right through the right side of the third receiving unit 470. The upper right end of the labeled antibody solution introduction unit 330 extends to the right below the first cleaning solution introduction unit 320 and is connected to the left end of the flow path 620. The flow path 620 extends to the right and connects to the common receiving portion 370. The lower left part of the common receiving part 370 is connected to the reaction part 380. The fourth receiving part 550 is a flow path that extends downward from the upper right part of the reaction part 380. The fourth receiving portion 550 is recessed rightward.

  The lower left part of the fourth receiving part 550 is connected to the measuring part 390. The measurement unit 390 is a part where a liquid including the sample liquid 91 is measured. The upper right part of the measurement part 390 is connected to the waste liquid part 700. The liquid flowing out from the measuring unit 390 to the waste liquid unit 700 is referred to as a waste liquid 85 (see state F5 in FIG. 5). The measurement unit 390 causes the waste liquid 85 to flow out to the waste liquid part 700 from the outflow end 391 that is the upper right end.

<5. Detailed Structure of Waste Liquid Unit 700>
With reference to FIG. 3, the detailed structure of the waste liquid part 700 is demonstrated. The waste liquid part 700 includes a first waste liquid part 710, a narrow channel 720, and a second waste liquid part 730. The first waste liquid part 710 extends downward from the upper right part of the measurement part 390. The narrow flow path 720 extends to the left from the lower end of the first waste liquid part 710 through the lower side of the measurement part 390. The second waste liquid portion 730 is a concave portion that is recessed upward from the left end portion of the narrow channel 720. The lower end portion 731 of the second waste liquid portion 730 is connected to the left end portion of the narrow channel 720. The upper end 732 of the second waste liquid unit 730 is between the measurement unit 390 and the reaction unit 380. The right end 733 of the second waste liquid part 730 is between the measurement part 390 and the narrow channel 720.

  A wall part separating the second waste liquid part 730 and the labeled antibody liquid introducing part 330 is referred to as a partition wall 741. A wall portion separating the second waste liquid portion 730 and the reaction portion 380 is referred to as a partition wall 742. A wall part separating the second waste liquid part 730 and the measurement part 390 is referred to as a partition wall 743. A wall part that separates the second waste liquid part 730 from the first waste liquid part 710 and the narrow channel 720 is referred to as a partition wall 744. The second waste liquid part 730 is arranged on the right side of the labeled antibody liquid introducing part 330 with the partition wall 741 interposed therebetween. The second waste liquid part 730 is disposed below the reaction part 380 with the partition wall 742 interposed therebetween. The second waste liquid unit 730 is disposed below the measurement unit 390 with the partition wall 743 interposed therebetween. The second waste liquid part 730 is disposed on the left side of the first waste liquid part 710 and on the upper side of the narrow channel 720 with the partition wall 744 interposed therebetween.

  A connection part between the first waste liquid part 710 and the narrow channel 720 is referred to as a connection part 751. The connecting portion 751 is a tapered wall surface that is inclined obliquely forward left and gradually decreases in the vertical direction from the rear surface of the lower left end portion of the first waste liquid portion 710 toward the narrow channel 720 toward the rear surface of the right end portion. . A connection part between the narrow channel 720 and the second waste liquid part 730 is referred to as a connection part 752. The connecting portion 752 is a stepped portion that protrudes forward from the rear surface of the lower end portion 731 toward the rear surface of the left end portion of the narrow channel 720. The narrow channel 720 is a channel formed by being surrounded by a wall surface 721 extending in the left-right direction between the connection portions 751 and 752.

  The measurement unit 390 described above is a region surrounded by a wall portion 392 that is recessed downward. The wall portion 392 includes a partition wall 743 and a part of the partition wall 745. The partition wall 745 is a wall part that separates the measurement part 390 and the first waste liquid part 710. A surface surrounding the measurement unit 390 in the partition wall 745 is a guide surface 393 that guides the liquid held in the measurement unit 390 to the downstream side. A surface surrounding the measurement unit 390 in the partition wall 743 is a facing surface 394 that faces the guide surface 393.

  The liquid that has flowed downstream from the measurement unit 390 can move downward in the first waste liquid unit 710 along the wall surface 701 that forms the right surface of the waste liquid unit 700. Further, the liquid can move from the first waste liquid part 710 to the second waste liquid part 730 along the wall surface 702 that forms the lower surface of the waste liquid part 700. That is, the liquid can move from the first waste liquid part 710 to the second waste liquid part 730 via the narrow channel 720. The liquid that has flowed into the second waste liquid part 730 can move upward from the lower end part 731 in the second waste liquid part 730. Furthermore, the liquid can move upward and to the right from the lower end portion 731 toward the right end portion 733 along the wall surface 703 that is the upper surface of the partition wall 744.

  The width of the narrow channel 720 in the vertical direction is small so that the liquid moving inside the narrow channel 720 contacts both the upper surface and the lower surface of the narrow channel 720. The width of the narrow channel 720 in the front-rear direction is small so that the liquid moving inside the narrow channel 720 contacts both the front surface and the rear surface of the narrow channel 720. That is, the narrow channel 720 is a narrow channel in which the liquid moves along the wall surface 721 while closing the channel cross section.

  In the partition wall 743, a communication path 800 extending from the upper end 732 to the upper right is formed. The communication path 800 is an air flow path connected from the second waste liquid part 730 to the measurement part 390. The communication path 800 passes through the partition wall 743 and the facing surface 394 and communicates with the measurement unit 390. The open end of the communication path 800 on the measurement unit 390 side is formed at the upper end portion of the facing surface 394 where the partition walls 742 and 743 are connected to each other.

  The waste liquid part 700 is a recess formed in the front surface 203 to a predetermined depth. The depth of the recess is synonymous with the width of the test chip 2 in the front-rear direction. In the present embodiment, the depth of the narrow channel 720 is smaller than at least the depths of the first waste liquid part 710 and the second waste liquid part 730. The depth of the first waste liquid part 710 and the depth of the second waste liquid part 730 are equal to each other. The depth of the communication path 800 and the depth of the narrow channel 720 are equal to each other. Note that the depth of the first waste liquid part 710 and the depth of the second waste liquid part 730 may be different from each other. The depth of the communication path 800 and the depth of the narrow channel 720 may be different from each other.

A downstream wall surface of the wall surfaces forming the reaction unit 380 is referred to as a guide surface 381. The inclination angles of the guide surfaces 381 and 393 are R7 and R8, respectively. In FIG. 4, as an example, the inclination angles R <b> 7 and R <b> 8 are indicated by angles formed between the guide surface 381 and the downward direction. The inclination angles R7 and R8 have the relationship of the following formula (2).
R5, R6, R8> R7 (2)
Note that R5, R6, and R8 have the same angle in the present embodiment, but may have different angles.

<6. Other structures of inspection chip 2>
As shown in FIG. 1, the support shaft 46 extending from the L-shaped plate 60 is vertically connected to the center of the rear surface of the plate member 19 via a mounting holder (not shown). As the support shaft 46 rotates, the inspection chip 2 rotates around the support shaft 46. When the inspection chip 2 is in the steady state shown in FIG. 2, the upper side 81 and the lower side 84 are orthogonal to the direction of gravity, the right side 82 and the left side 83 are parallel to the direction of gravity, and the left side 83 is the right side. It is arranged closer to the main shaft 57 than the portion 82. In a state where the inspection chip 2 in the steady state is arranged at the measurement position, the inspection apparatus 1 performs inspection by optical measurement by allowing the measurement light connecting the light source 71 and the optical sensor 72 to pass through the measurement unit 390.

<7. Example of inspection method>
An inspection method using the inspection apparatus 1 and the inspection chip 2 will be described. As shown in FIG. 2, the stop liquid 96 is injected into the stop liquid introducing section 360 via the injection path 530. The substrate solution 95 is injected into the substrate solution introduction unit 350 via the injection path 520. The second cleaning liquid 94 is injected into the second cleaning liquid introduction unit 340 via the injection path 510. The labeled antibody solution 93 is injected into the labeled antibody solution introduction unit 330 via the injection path 500. The first cleaning liquid 92 is injected into the first cleaning liquid introduction unit 320 via the injection path 490. The sample liquid 91 is injected into the sample liquid introducing section 310 via the injection path 480. Other methods may be used for the arrangement of each liquid.

  The user attaches the inspection chip 2 to a mounting holder (not shown) and inputs a processing start command from the operation unit 104. As a result, the CPU 101 executes the centrifugal process shown in FIG. 4 based on the control program stored in the ROM 103. In the centrifugal process, the CPU 101 controls the spindle motor 35 via the revolution controller 97 to execute each operation of starting the revolution of the inspection chip 2, controlling the revolution speed, and stopping the revolution. In the present embodiment, the CPU 101 revolves the inspection chip 2 around the vertical axis A1 in a clockwise direction in plan view (see FIG. 1). The CPU 101 controls the revolution speed of the inspection chip 2 by controlling the rotation speed per unit time of the spindle motor 35.

  In the centrifugal process, the CPU 101 performs each operation of changing the rotation angle of the test chip 2 by driving and controlling the stepping motor 51 via the rotation controller 98. In the following description, the rotation angle of the test chip 2 in the steady state shown in FIG. The rotation angle of the inspection chip 2 rotated counterclockwise by m degrees from the steady state around the horizontal axis A2 in the front view is defined as m degrees. For example, the rotation angle of the inspection chip 2 rotated 90 degrees counterclockwise from the steady state is 90 degrees. In the present embodiment, when changing the CPU 101 to increase the rotation angle, the CPU 101 rotates the inspection chip 2 counterclockwise around the horizontal axis A2 in front view. When changing the CPU 101 so as to decrease the rotation angle, the CPU 101 rotates the inspection chip 2 clockwise about the horizontal axis A2 in front view.

  As shown in FIG. 4, first, the CPU 101 executes a first liquid feeding process (S1). In the first liquid feeding process, the revolution of the inspection chip 2 is started, and the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 0 degree to the first rotation angle. The first rotation angle is the rotation angle of the inspection chip 2 where the centrifugal force acts perpendicularly to the first wall surface 501 (see FIG. 2).

  In the first liquid feeding process, the centrifugal force X1 is applied to the inspection chip 2 having the first rotation angle for a predetermined time. At this time, as shown in a state F1 in FIG. 5, the centrifugal force X1 acts on the test chip 2 in a direction perpendicular to the first wall surface 501. The sample solution 91 moves from the sample solution introduction unit 310 to the common receiving unit 370 via the flow path 610 by the action of the centrifugal force X1. According to the relationship of the above formula (1), the first cleaning solution 92, the labeled antibody solution 93, the second cleaning solution 94, the substrate solution 95, and the stop solution 96 are respectively a first cleaning solution introducing unit 320, a labeled antibody solution introducing unit 330, The second cleaning liquid introduction unit 340, the substrate solution introduction unit 350, and the stop liquid introduction unit 360 are held.

  Next, the CPU 101 executes the first reaction process (S2). In the first reaction step, the revolution speed is lowered until the centrifugal force X21 acts on the inspection chip 2. The centrifugal force X21 has a magnitude equal to or smaller than the centrifugal force X1, and is about ½ of the centrifugal force X1 in the present embodiment. Further, the rotation angle of the inspection chip 2 is changed from the first rotation angle to 90 degrees.

  In the first reaction step, the centrifugal force X21 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in the state F <b> 2 of FIG. 5, the centrifugal force X <b> 21 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. The sample liquid 91 moves from the common receiving part 370 to the reaction part 380 by the action of the centrifugal force X21. In the reaction unit 380, the test target substance contained in the sample solution 91 is combined with the immobilized antibody. A conjugate of the test substance and the immobilized antibody is referred to as a first conjugate.

  Next, the CPU 101 executes a second liquid feeding process (S3). In the second liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to the second rotation angle. The second rotation angle is the rotation angle of the inspection chip 2 where the centrifugal force acts perpendicularly to the second wall surface 502 (see FIG. 2).

  In the second liquid feeding step, the centrifugal force X1 is applied to the inspection tip 2 having the second rotation angle for a predetermined time. At this time, the centrifugal force X1 acts on the test chip 2 in a direction perpendicular to the second wall surface 502, as shown in a state F3 in FIG. Due to the action of the centrifugal force X1, the first cleaning liquid 92 moves from the first cleaning liquid introduction section 320 to the common receiving section 370 via the flow path 610, and the sample liquid 91 moves from the reaction section 380 to the fourth receiving section 550. To do. According to the relationship of the above formula (1), the labeled antibody solution 93, the second washing solution 94, the substrate solution 95, and the stop solution 96 are respectively labeled antibody solution introduction unit 330, second washing solution introduction unit 340, and substrate solution introduction unit 350. And the stop liquid introduction unit 360.

  Next, the CPU 101 executes a first cleaning process (S4). In the first cleaning step, the revolution speed is lowered until the centrifugal force X31 acts on the inspection chip 2. The centrifugal force X31 has a magnitude less than the centrifugal force X21, more preferably larger than the centrifugal forces X32 and X33 described later, and is about ½ of the centrifugal force X21 in this embodiment. Further, the rotation angle of the inspection chip 2 is changed from the second rotation angle to 90 degrees.

  In the first cleaning step, the centrifugal force X31 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in a state F4 in FIG. 5, the centrifugal force X31 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. Due to the action of the centrifugal force X31, the first cleaning liquid 92 moves from the common receiving part 370 to the reaction part 380, and the sample liquid 91 moves from the fourth receiving part 550 to the measuring part 390. The first cleaning unit 92 that has moved to the reaction unit 380 performs the first cleaning of the reaction unit 380. Specifically, in the reaction unit 380, the components of the sample solution 91 that are not bound to the immobilized antibody are removed by the first cleaning solution 92. That is, components other than the first combined body remaining in the reaction unit 380 are removed by the first cleaning liquid 92.

  Next, the CPU 101 executes a third liquid feeding process (S5). In the third liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to 0 degrees. In the first liquid feeding process, the centrifugal force X1 is applied to the inspection chip 2 having a rotation angle of 0 degree for a predetermined time. At this time, as shown in a state F5 in FIG. 5, the centrifugal force X1 acts on the test chip 2 from the left side portion 83 toward the right side portion 82. By the action of the centrifugal force X1, each liquid moves as follows.

  The first cleaning liquid 92 moves from the reaction unit 380 to the fourth receiving unit 550. The labeled antibody solution 93 moves from the labeled antibody solution introducing unit 330 to the common receiving unit 370. The second cleaning liquid 94 moves from the second cleaning liquid introduction unit 340 to the third receiving unit 470. The substrate solution 95 moves from the substrate solution introduction unit 350 to the second receiving unit 460. The stop liquid 96 moves from the stop liquid introducing unit 360 to the first receiving unit 450. The sample liquid 91 moves from the measurement unit 390 to the first waste liquid unit 710 as the waste liquid 85. At this time, the waste liquid 85 is held in the right part of the first waste liquid part 710.

  Next, the CPU 101 executes the second reaction step (S6). In the second reaction step, the revolution speed is lowered until the centrifugal force X22 acts on the inspection chip 2. Centrifugal force X22 has a magnitude of centrifugal force X1 or less, and preferably has a magnitude of centrifugal force X21 or less. The centrifugal force X22 of this embodiment is about 2/3 of the centrifugal force X21. Further, the rotation angle of the inspection chip 2 is changed from 0 degrees to 90 degrees. In the second reaction step, the centrifugal force X22 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in a state F6 in FIG. 5, the centrifugal force X22 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. By the action of the centrifugal force X22, each liquid moves as follows.

  The first cleaning liquid 92 moves from the fourth receiving unit 550 to the measuring unit 390. The labeled antibody solution 93 moves from the common receiving unit 370 to the reaction unit 380. The second cleaning liquid 94 moves from the third receiving part 470 to the labeled antibody liquid introducing part 330. The substrate solution 95 moves from the second receiving part 460 to the second cleaning liquid introducing part 340. The stop liquid 96 moves from the first receiving unit 450 to the substrate solution introducing unit 350. In the reaction unit 380, the enzyme-labeled antibody contained in the labeled antibody solution 93 specifically binds to the first conjugate. A conjugate of the enzyme-labeled antibody and the first conjugate is referred to as a second conjugate.

  The waste liquid 85 moves downward in the first waste liquid part 710 along the wall surface 701 (see FIG. 3). Further, a part of the waste liquid 85 moves leftward in the narrow channel 720 along the wall surface 702 (see FIG. 3) and flows into the second waste liquid part 730. As a result, the waste liquid 85 is held at the lower part of the first waste liquid part 710, the narrow channel 720, and the lower part of the second waste liquid part 730 by the action of the centrifugal force X22. The liquid level 851 of the waste liquid 85 in the second waste liquid part 730 is aligned with the liquid level 852 of the waste liquid 85 in the first waste liquid part 710 in a direction orthogonal to the centrifugal force direction. The liquid level 851 is upstream of the lower end portion 731 (see FIG. 3) in the second waste liquid portion 730 in the centrifugal force direction.

  Next, the CPU 101 executes a fourth liquid feeding process (S7). In the fourth liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to the third rotation angle. The third rotation angle is the rotation angle of the inspection chip 2 where the centrifugal force acts perpendicularly to the guide surface 381 (see FIG. 2). In the third liquid feeding step, the centrifugal force X1 is applied to the inspection chip 2 having the third rotation angle for a predetermined time. At this time, as shown in a state F7 in FIG. 6, the centrifugal force X1 acts on the test chip 2 in the direction perpendicular to the guide surface 381. By the action of the centrifugal force X1, each liquid moves as follows.

  The labeled antibody solution 93 moves from the reaction unit 380 to the fourth receiving unit 550. Among the waste liquids 85 in the second waste liquid part 730, the waste liquid 85 located above the lower end part 731 is referred to as a target waste liquid. The target waste liquid moves to the right end portion 733 along the wall surface 703 (see FIG. 3) and is held at the right portion of the second waste liquid portion 730. The waste liquid 85 in the waste liquid part 700 is moved and held along the wall surface 702 to the lower right part of the first waste liquid part 710 except for the target waste liquid.

  According to the relationship of the above formula (2), the first cleaning liquid 92, the second cleaning liquid 94, the substrate solution 95, and the stop liquid 96 are the measurement unit 390, the labeled antibody solution introduction unit 330, the second cleaning solution introduction unit 340, the substrate, respectively. It is held in the solution introduction part 350. However, when the test chip 2 is at the third rotation angle, the amount of liquid that can be held in the labeled antibody liquid introduction unit 330 by the action of centrifugal force is smaller than the total amount of the second cleaning liquid 94. Accordingly, a part of the second washing liquid 94 in the labeled antibody solution introduction unit 330 overflows from the labeled antibody solution introduction unit 330 and moves to the common receiving unit 370 by the action of the centrifugal force X1. In the present embodiment, a part of the second cleaning liquid 94 moves from the labeled antibody liquid introducing unit 330 to the common receiving unit 370.

  Next, the CPU 101 executes a second cleaning process (S8). In the second cleaning step, the revolution speed is lowered until the centrifugal force X32 acts on the inspection chip 2. The centrifugal force X32 has a magnitude smaller than the centrifugal force X21, and is approximately the same as the centrifugal force X31 in this embodiment. Further, the rotation angle of the inspection chip 2 is changed from the third rotation angle to 90 degrees. In the second cleaning step, the centrifugal force X32 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in a state F8 in FIG. 6, the centrifugal force X32 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. By the action of the centrifugal force X32, each liquid moves as follows.

  The second cleaning liquid 94 in the common receiving unit 370 moves to the reaction unit 380. The second cleaning unit 94 that has moved to the reaction unit 380 performs the second cleaning of the reaction unit 380. Specifically, in the reaction unit 380, the components of the labeled antibody solution 93 that are not bound to the first conjugate are removed by the second washing solution 94. That is, components other than the second conjugate remaining in the reaction unit 380 are removed by the second cleaning liquid 94. The labeled antibody solution 93 moves from the fourth receiving unit 550 to the measuring unit 390. In the measurement unit 390, the labeled antibody solution 93 and the first cleaning solution 92 are mixed to generate a mixed solution 86. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F6 in FIG.

  Next, the CPU 101 executes the fifth liquid feeding process (S9). In the fifth liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to 0 degrees. In the fifth liquid feeding process, the centrifugal force X1 is applied to the inspection chip 2 having a rotation angle of 0 degree for a predetermined time. At this time, as shown in a state F9 in FIG. 6, the centrifugal force X1 acts on the test chip 2 from the left side portion 83 toward the right side portion 82. By the action of the centrifugal force X1, each liquid moves as follows.

  The second cleaning liquid 94 in the reaction unit 380 moves to the fourth receiving unit 550. The second cleaning solution 94 in the labeled antibody solution introduction unit 330 moves to the common receiving unit 370. The substrate solution 95 moves from the second cleaning liquid introducing unit 340 to the third receiving unit 470. The stop liquid 96 moves from the substrate solution introducing unit 350 to the second receiving unit 460. The mixed liquid 86 moves from the measurement unit 390 to the first waste liquid unit 710 as the waste liquid 85. Thereby, the waste liquid 85 stored in the waste liquid part 700 increases. The target waste liquid moves to the right end 733 along the wall surface 703 and is held on the right part of the second waste liquid part 730. The waste liquid 85 in the waste liquid part 700 is moved and held along the wall surface 702 to the right part of the first waste liquid part 710 except for the target waste liquid.

  Next, the CPU 101 executes a third cleaning process (S10). In the third cleaning step, the revolution speed is lowered until the centrifugal force X33 acts on the inspection chip 2. The centrifugal force X33 is less than the centrifugal force X21, and preferably greater than the centrifugal force X32. The centrifugal force X33 of this embodiment is about 3/2 of the centrifugal force X32. Further, the rotation angle of the inspection chip 2 is changed from 0 degrees to 90 degrees. In the third cleaning step, the centrifugal force X33 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in a state F10 in FIG. 6, the centrifugal force X33 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. By the action of the centrifugal force X33, each liquid moves as follows.

  The second cleaning liquid 94 in the fourth receiving unit 550 moves to the measuring unit 390. The second cleaning liquid 94 in the common receiving unit 370 moves to the reaction unit 380. The second cleaning liquid 94 moved to the reaction unit 380 performs the third cleaning of the reaction unit 380 in the same manner as the second cleaning of the reaction unit 380. The substrate solution 95 moves from the third receiving unit 470 to the labeled antibody solution introducing unit 330. The stop liquid 96 moves from the second receiving part 460 to the second cleaning liquid introducing part 340. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F8 in FIG. At this time, the liquid levels 851 and 852 are upstream of the state F8 in the centrifugal force direction.

  Next, the CPU 101 executes a sixth liquid feeding process (S11). In the sixth liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to 0 degrees. In the sixth liquid feeding process, the centrifugal force X1 is applied to the inspection chip 2 having a rotation angle of 0 degree for a predetermined time. At this time, as shown in a state F11 in FIG. 6, the centrifugal force X1 acts on the test chip 2 from the left side portion 83 toward the right side portion 82. By the action of the centrifugal force X1, each liquid moves as follows.

  The second cleaning liquid 94 in the reaction unit 380 moves to the fourth receiving unit 550. The substrate solution 95 moves from the labeled antibody solution introduction unit 330 to the common receiving unit 370. The stop liquid 96 moves from the second cleaning liquid introducing unit 340 to the third receiving unit 470. The second cleaning liquid 94 in the measurement unit 390 moves to the first waste liquid unit 710 as the waste liquid 85. Thereby, the waste liquid 85 stored in the waste liquid part 700 increases. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F9 in FIG. At this time, the liquid amount of the waste liquid 85 held in each of the first waste liquid part 710 and the second waste liquid part 730 is larger than that in the state F9.

  Next, the CPU 101 executes a third reaction step (S12). In the third reaction step, the revolution speed is lowered until the centrifugal force X23 acts on the inspection chip 2. Centrifugal force X23 has a magnitude of centrifugal force X1 or less, and preferably has a magnitude of centrifugal force X21 or less. The centrifugal force X23 of the present embodiment is approximately the same as the centrifugal force X22. Further, the rotation angle of the inspection chip 2 is changed from 0 degrees to 90 degrees. In the third reaction step, the centrifugal force X23 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time. At this time, as shown in a state F <b> 12 of FIG. 6, the centrifugal force X <b> 23 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. By the action of the centrifugal force X23, each liquid moves as follows.

  The second cleaning liquid 94 moves from the fourth receiving unit 550 to the measuring unit 390. The substrate solution 95 moves from the common receiving unit 370 to the reaction unit 380. In the reaction unit 380, the substrate solution 95 reacts with the enzyme-labeled antibody contained in the second conjugate. The stop solution 96 moves from the third receiving unit 470 to the labeled antibody solution introducing unit 330. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F10 of FIG. At this time, the liquid levels 851 and 852 are upstream of the state F10 in the centrifugal force direction.

  Next, the CPU 101 executes a seventh liquid feeding process (S13). In the seventh liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to 0 degrees. In the seventh liquid feeding process, the centrifugal force X1 is applied to the inspection chip 2 having a rotation angle of 0 degree for a predetermined time. At this time, as shown in the state F13 of FIG. 7, the centrifugal force X1 acts on the test chip 2 from the left side portion 83 toward the right side portion 82. By the action of the centrifugal force X1, each liquid moves as follows.

  The substrate solution 95 moves from the reaction unit 380 to the fourth receiving unit 550. The stop solution 96 moves from the labeled antibody solution introduction unit 330 to the common receiving unit 370. The second cleaning liquid 94 in the measurement unit 390 moves to the first waste liquid unit 710 as the waste liquid 85. Thereby, the waste liquid 85 stored in the waste liquid part 700 increases. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F11 of FIG. At this time, the liquid amount of the waste liquid 85 held in each of the first waste liquid part 710 and the second waste liquid part 730 is larger than that in the state F11.

  Next, the CPU 101 executes a fourth reaction process (S14). In the fourth reaction step, the revolution speed is lowered until the centrifugal force X24 acts on the test chip 2. The centrifugal force X24 has a magnitude of not more than the centrifugal force X1, and preferably has a magnitude of not more than the centrifugal force X21. The centrifugal force X24 of this embodiment is approximately the same as the centrifugal force X22. Further, the rotation angle of the inspection chip 2 is changed from 0 degrees to 90 degrees. In the fourth reaction step, the centrifugal force X24 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time.

  At this time, as shown in a state F14 in FIG. 7, the centrifugal force X24 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. By the action of the centrifugal force X24, each liquid moves as follows. The substrate solution 95 moves from the fourth receiving unit 550 to the measuring unit 390. The stop liquid 96 moves from the common receiving unit 370 to the reaction unit 380. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F12 of FIG. At this time, the liquid levels 851 and 852 are upstream of the state F12 in the centrifugal force direction.

  Next, the CPU 101 executes an eighth liquid feeding process (S15). In the eighth liquid feeding step, the revolution speed is increased until the centrifugal force X1 acts on the inspection chip 2. Further, the rotation angle of the inspection chip 2 is changed from 90 degrees to the third rotation angle. In the eighth liquid feeding step, the centrifugal force X1 is applied to the inspection tip 2 having the third rotation angle for a predetermined time.

  At this time, as shown in a state F15 in FIG. 7, the centrifugal force X1 acts on the test chip 2 in a direction perpendicular to the guide surface 381. Due to the action of the centrifugal force X1, the stop liquid 96 moves from the reaction unit 380 to the fourth receiving unit 550. The substrate solution 95 is held in the measurement unit 390 according to the relationship of the above formula (2). In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F7 in FIG.

  Next, the CPU 101 executes a fifth reaction step (S16). In the fifth reaction step, the revolution speed is lowered until the centrifugal force X25 acts on the test chip 2. Centrifugal force X25 has a magnitude of centrifugal force X1 or less, and preferably has a magnitude of centrifugal force X21 or less. The centrifugal force X25 of the present embodiment is approximately the same as the centrifugal force X22. Further, the rotation angle of the inspection chip 2 is changed from 0 degrees to 90 degrees. In the fifth reaction step, the centrifugal force X25 is applied to the inspection chip 2 having a rotation angle of 90 degrees for a predetermined time.

  At this time, as shown in a state F <b> 16 in FIG. 7, the centrifugal force X <b> 24 acts on the test chip 2 from the upper side portion 81 toward the lower side portion 84. Due to the action of the centrifugal force X25, the stop liquid 96 moves from the fourth receiving part 550 to the measuring part 390. In the measurement unit 390, the stop solution 96 is mixed with the substrate solution 95, and the progress of the enzyme reaction of the substrate solution 95 is stopped. The substrate solution 95 mixed with the stop solution 96 is referred to as a measurement solution 87. In the waste liquid part 700, the waste liquid 85 moves in the same manner as in the state F14 of FIG.

  After executing the fifth reaction step, the CPU 101 lowers the revolution speed to 0, changes the rotation angle from 90 degrees to 0 degrees, and ends the centrifugation process. As shown in a state F <b> 16 in FIG. 7, gravity G acts on the inspection chip 2 from the upper side portion 81 toward the lower side portion 84. The measurement solution 87 is held in the measurement unit 390 due to the gravity G. After executing the centrifugal process, the CPU 101 revolves the inspection chip 2 to the measurement position.

  As shown in FIG. 1, the measurement controller 99 causes the measurement light 87 to pass through the measurement solution 87 stored in the measurement unit 390 by causing the light source 71 to emit light. The CPU 101 performs optical measurement of the measurement solution 87 based on the change amount of the measurement light received by the optical sensor 72 and acquires measurement data. The CPU 101 calculates the measurement result of the measurement solution 87 based on the acquired measurement data, and displays the calculation result on the display 106. Note that the measurement method of the measurement solution 87 is not limited to optical measurement, and other methods may be used.

<8. Control Mode of Centrifugal Force in Centrifugal Processing>
With reference to FIG. 8, the control aspect of the centrifugal force in a centrifugation process (refer FIG. 4) is demonstrated. FIG. 8 is an enlarged view of the vicinity of the reaction unit 380 in a front view of a cross section of a virtual plane passing through the center in the front-rear direction in the test chip 2 having a rotation angle of 90 degrees where the centrifugal force X acts. In FIG. 8, it is assumed that a liquid (not shown) is stored in the reaction unit 380. Moreover, in the reaction part 380, the liquid level C1-C4 of the liquid which changes according to the magnitude | size of the centrifugal force X is shown with a virtual line. The liquid levels C1 to C4 are liquid levels of the same amount of liquid.

  In the centrifugation process, a sample solution 91, a labeled antibody solution 93, and a substrate solution 95, which are liquids involved in the reaction, and a first washing solution 92 and a second washing solution 94, which are liquids not involved in the reaction, are used. Due to the action of the centrifugal forces X21 to X23, the liquid involved in the reaction is held in the predetermined part, whereby the predetermined reaction is performed. Due to the action of the centrifugal forces X31 to X33, a liquid that does not participate in the reaction is held at a predetermined site, so that a process different from the reaction is performed. In this embodiment, the predetermined part is the reaction part 380, and the process different from the reaction is a cleaning process. Hereinafter, the centrifugal forces X21 to X23 are collectively referred to as centrifugal force X2. The centrifugal force X2 may include centrifugal forces X24 and X25. Further, the centrifugal forces X31 to X33 are collectively referred to as centrifugal force X3.

(1) The centrifugal force X2 is larger than the centrifugal force X3. Specifically, each of the centrifugal forces X21 to X23 is greater than any of the centrifugal forces X31 to X33. In this example, in the state where the centrifugal force X21 is applied to the test chip 2 shown in FIG. 8, the liquid level of the liquid in the reaction unit 380 is the same surface state as the liquid level C1. The liquid level C1 has a planar shape orthogonal to the centrifugal force direction.

  In a state where any one of the centrifugal forces X22 and X23 is applied to the inspection chip 2 shown in FIG. 8, the liquid in the reaction unit 380 spreads slightly along the wall surface of the reaction unit 380 due to surface tension. At this time, the liquid level in the reaction unit 380 is in the same surface state as the liquid level C2. The liquid level C2 is a curved surface that is recessed downstream in the centrifugal force direction as compared with the liquid level C1. When the liquid levels C1 and C2 are liquid levels of the same amount of liquid, the edge of the liquid level C2 is upstream of the edge of the liquid level C1 in the centrifugal force direction. In this case, the liquid on the liquid surface C2 has a larger contact area with the wall surface of the reaction unit 380 than the liquid on the liquid surface C1.

  In the state in which the centrifugal force X33 is applied to the inspection chip 2 shown in FIG. 8, the liquid in the reaction unit 380 is caused by the surface tension of the reaction unit 380 than in the state in which any one of the centrifugal forces X22 and X23 is applied. It is easy to spread along the wall. At this time, the liquid level in the reaction unit 380 is in the same surface state as the liquid level C3. The liquid level C3 is a curved surface that is greatly recessed downstream in the centrifugal force direction as compared with the liquid level C2. When the liquid levels C2 and C3 are liquid levels of the same amount of liquid, the edge of the liquid level C3 is upstream of the edge of the liquid level C2 in the centrifugal force direction. In this case, the liquid on the liquid surface C3 has a larger contact area with the wall surface of the reaction unit 380 than the liquid on the liquid surface C2.

  In the state where any one of the centrifugal forces X31 and X32 is applied to the inspection chip 2 shown in FIG. 8, the liquid in the reaction unit 380 is caused by the surface tension of the reaction unit 380 than in the state where the centrifugal force X33 is applied. It is easy to spread along the wall. At this time, the liquid level in the reaction unit 380 is in the same surface state as the liquid level C4. The liquid surface C4 is a curved surface that is greatly recessed downstream in the centrifugal force direction as compared with the liquid surface C3. When the liquid surfaces C3 and C4 are liquid surfaces of the same amount of liquid, the edge of the liquid surface C4 is located upstream of the edge of the liquid surface C3 in the centrifugal force direction. In this case, the liquid on the liquid surface C4 has a larger contact area with the wall surface of the reaction unit 380 than the liquid on the liquid surface C3.

  That is, each of the liquid levels C3 and C4 based on the centrifugal force X3 is in a state in which the ratio of contact with the wall surface of the reaction unit 380 is larger than the liquid levels C1 and C2 based on the centrifugal force X2. . Therefore, in the first cleaning step of S4 (state F4 in FIG. 5), the components of the sample liquid 91 remaining on the wall surface of the reaction unit 380 can be cleaned with the first cleaning liquid 92 having a smaller liquid volume than the sample liquid 91.

  More specifically, in the first reaction step S2 (state F2 in FIG. 5), the liquid surface of the sample liquid 91 is held in the same surface state as the liquid surface C1 by the centrifugal force X21. Next, in the first cleaning step of S4 (state F4 in FIG. 5), the liquid level of the first cleaning liquid 92 is maintained in the same surface state as the liquid level C4 by the centrifugal force X31. At this time, even when the amount of the first cleaning liquid 92 is smaller than the amount of the sample liquid 91, the edge of the liquid surface of the first cleaning liquid 92 is upstream of the edge of the liquid surface of the sample liquid 91 in the centrifugal force direction. If it exists in the side, the 1st washing | cleaning liquid 92 can remove the component of the sample liquid 91 which remains on the wall surface of the reaction part 380. FIG.

  Similarly, in the second washing step of S8 (state F8 in FIG. 6) and the third washing step of S10 (state F10 in FIG. 6), the reaction part is treated by the second washing liquid 94 having a smaller amount than the labeled antibody solution 93. The components of the labeled antibody solution 93 remaining on the wall surface of 380 can be removed. Further, the components of the labeled antibody solution 93 remaining on the wall surface of the reaction unit 380 are reliably washed by two washing steps (second washing step and third washing step).

(2) The centrifugal force X33 is equal to or greater than the centrifugal force X32. In this example, the centrifugal force X33 is larger than the centrifugal force X32. In the second cleaning step, the liquid level of the second cleaning liquid 94 is maintained in the same surface state as the liquid level C4 by the centrifugal force X32. The liquid level C4 is in a state in which the ratio of the liquid level C1 to C4 contacting the wall surface of the reaction unit 380 is the largest with respect to the liquid level. When the liquid level is the same as the liquid level C4, the contact area between the second cleaning liquid 94 and the wall surface of the reaction unit 380 is large, so that a wide range of the reaction unit 380 can be cleaned.

  Next, in the third cleaning step, the liquid level of the second cleaning liquid 94 is held in the state of the liquid level C3 by the centrifugal force X33. The contact area between the second cleaning liquid 94 and the wall surface of the reaction unit 380 is smaller than that in the second cleaning step. On the other hand, the wall surface of the reaction part 380 cleaned by the second cleaning step is wet with the second cleaning liquid 94. Therefore, in the third cleaning step, the second cleaning liquid 94 easily spreads along the wall surface of the reaction unit 380 and easily flows out of the reaction unit 380. On the other hand, since the centrifugal force X33 is larger than the centrifugal force X32, the second cleaning liquid 94 can be reliably held in the reaction unit 380. The centrifugal forces X32 and X33 may have the same magnitude.

  The centrifugal force X31 is preferably larger than the centrifugal forces X32 and X33. In the present embodiment, the cleaning accuracy of the second and third cleaning steps to be executed later has a greater influence on the liquid reaction test result than the cleaning accuracy of the first cleaning step to be executed first. By making the centrifugal force X31 larger than the centrifugal forces X32 and X33, the second and third washing steps can wash a wider area of the reaction unit 380 than the first washing step. Therefore, an accurate test result regarding the liquid reaction can be obtained while suppressing the amount of the second cleaning liquid 94 used.

(3) The centrifugal force X1 is a centrifugal force for moving the liquid. The centrifugal force X2 is equal to or less than the centrifugal force X1. That is, the centrifugal force X1 is the largest among the centrifugal forces X1, X2, and X3. Thereby, in each conveyance process (S1, S3, S5, S7, S9, S11, S13, S15), the liquid to be moved can be accurately moved to the target position without causing a liquid residue. Further, in a state where the centrifugal force X1 is applied to the test chip 2, the liquid level of the liquid becomes a planar shape orthogonal to the centrifugal force direction, like the liquid level C1. Therefore, since the contact area between the liquid to be moved and the wall surface forming the liquid flow path 25 can be suppressed, the transport accuracy of other liquids can be improved.

  In this example, the centrifugal forces X2 and X3 are both smaller than the centrifugal force X1. Therefore, the revolution speed of each reaction process (S2, S6, S12, S14, S16) and the revolution speed of each cleaning process (S4, S8, S10) are all smaller than the revolution speed of each conveyance process. Thus, the energy consumption at the time of the centrifugation process of the test | inspection apparatus 1 can be reduced by suppressing the revolution speed in processes other than each conveyance process. The centrifugal force X2 may be the same magnitude as the centrifugal force X1.

(4) The centrifugal force X21 is greater than or equal to the centrifugal forces X22 and X23. In the first reaction step (S2), the test target substance contained in the sample solution 91 is combined with the immobilized antibody in the reaction unit 380. At this time, the larger the contact area between the sample solution 91 and the reaction unit 380, the greater the amount of first conjugate produced. If the amount of the first conjugate produced in the first reaction step does not match the expected amount, the measurement accuracy may be adversely affected.

  In this example, the centrifugal force X21 is the largest among the centrifugal forces X21 to X23. When the centrifugal force X21 is applied in the first reaction step, the liquid surface of the sample liquid 91 in the reaction unit 380 becomes a planar shape orthogonal to the centrifugal force direction. Thereby, the contact area of the sample liquid 91 and the reaction part 380 can be controlled to a predetermined area suitable for obtaining accurate measurement accuracy. Since the production amount of the first conjugate is controlled to a predetermined amount suitable for obtaining accurate measurement accuracy, the measurement accuracy can be improved.

  On the other hand, in the second reaction step (S6), the amount of the labeled antibody solution 93 that is a reactant is excessive with respect to the amount of the first conjugate that is a reactant. Therefore, in the second reaction step, the necessity for accurately controlling the contact area between the labeled antibody solution 93 and the wall surface of the reaction unit 380 is relatively low. Similarly, in the third reaction step (S12), the amount of the substrate solution 95 that is a reactant is excessive with respect to the amount of the second conjugate that is a reactant. Therefore, in the third reaction step, the necessity of accurately controlling the contact area between the substrate solution 95 and the wall surface of the reaction unit 380 is relatively low.

  Therefore, in the second reaction step and the third reaction step, the necessity for controlling the liquid level with high accuracy as in the first reaction step is relatively low. In this example, since each of the centrifugal forces X22 and X23 is smaller than the centrifugal force X21, it is possible to reduce energy consumption during the centrifugal processing of the inspection apparatus 1. The centrifugal force X21 may be as large as at least one of the centrifugal forces X22 and X23. The centrifugal forces X22 and X23 may be the same size or different from each other.

<9. Example of operation of this embodiment>
(1) In each step of the centrifugal treatment (see FIG. 4), the liquid is operated as follows by applying an acceleration to the inspection chip 2. In the present embodiment, each step of the centrifugal process is executed by causing the inspection device 1 to apply a centrifugal force as an acceleration to the inspection chip 2 and adjusting the direction in which the centrifugal force acts. Hereinafter, the sample solution introduction unit 310, the first washing solution introduction unit 320, the labeled antibody solution introduction unit 330, the second washing solution introduction unit 340, the substrate solution introduction unit 350, and the stop solution introduction unit 360 are collectively referred to as each liquid. It is called an introduction section that is an area to be introduced.

  First, in the first liquid feeding step (S1), the sample liquid 91 that is a liquid involved in the reaction is moved downstream from the introduction portion. Next, in the first reaction step (S2), the sample solution 91 is held in the reaction unit 380. Next, in the second liquid feeding step (S3), the sample liquid 91 is moved downstream from the reaction part 380, and the first cleaning liquid 92 that is a liquid not involved in the reaction is moved downstream from the introduction part. Next, in the first cleaning step (S4), the first cleaning liquid 92 is held in the reaction unit 380. The centrifugal force X21 in the first reaction step is larger than the centrifugal force X31 in the first cleaning step. Thereby, in the surface tension between the sample liquid 91 and the reaction part 380 held in the first reaction step, and the surface tension between the first cleaning liquid 92 and the reaction part 380 held in the first cleaning step, In the former, the force in the direction offset by acceleration is more likely to work.

  That is, when the liquid amounts of the sample liquid 91 and the first cleaning liquid 92 are the same, the contact area between the first cleaning liquid 92 and the reaction unit 380 in the first cleaning process reacts with the sample liquid 91 in the first reaction process. The contact area with the portion 380 is larger. Even when the amount of the first cleaning liquid 92 is smaller than the amount of the sample liquid 91, the first cleaning liquid 92 can contact the entire region of the reaction unit 380 that is in contact with the sample liquid 91. Therefore, an accurate test result relating to the liquid reaction can be obtained while suppressing the amount of the first cleaning liquid 92 that is not involved in the reaction.

(2) In the first reaction step (S2), the sample solution 91 is reacted with the immobilized antibody arranged in the reaction unit 380. In the first cleaning step (S4), the reaction section 380 is cleaned by the first cleaning liquid 92. Thereby, in the process after a 1st washing | cleaning process, the liquid can be made to react correctly in the process after the 1st washing | cleaning process, suppressing the usage-amount of the 1st washing | cleaning liquid 92 which is not concerned in reaction.

(3) In the first reaction step (S2), a first conjugate in which the test substance and the immobilized antibody are bound is generated. In the first washing step (S4), components other than the first combined body remaining in the reaction unit 380 are removed. Next, in the third liquid feeding step (S5), the first cleaning liquid 92 is moved downstream from the reaction part 380, and the labeled antibody liquid 93 is moved downstream from the introduction part. Next, in the second reaction step (S6), the labeled antibody solution 93 is held in the reaction unit 380, and a second conjugate in which the enzyme-labeled antibody and the first conjugate are specifically bound is generated. Next, in the fourth liquid feeding step (S7) and the fifth liquid feeding step (S9), the labeled antibody solution 93 is moved downstream from the reaction part 380, and the second cleaning liquid 94 is moved downstream from the introduction part. The

  Next, in the second cleaning step (S8) and the third cleaning step (S10), the second cleaning liquid 94 is held in the reaction unit 380, and components other than the second conjugate remaining in the reaction unit 380 are removed. Next, in the sixth liquid feeding step (S11), the second cleaning liquid 94 is moved downstream from the reaction part 380, and the substrate solution 95 is moved downstream from the introduction part. Next, in the third reaction step (S12), the substrate solution 95 is held in the reaction unit 380, and the substrate solution 95 is reacted with the second conjugate. The centrifugal forces X21, X22, X23 in the first to third reaction steps (S2, S6, S12) are more than the centrifugal forces X31, X32, X33 in the first to third washing steps (S4, S8, S10). large.

  That is, the centrifugal force X2 of each process in which the first liquid is reacted in the reaction unit 380 is larger than the centrifugal force X3 of each process of washing the reaction part 380 with the second liquid. Thereby, the surface tension between the first liquid and the reaction part 380 in each of the first to third reaction steps, and the surface between the second liquid and the reaction part 380 in each of the first to third cleaning steps. With tension, the former tends to work in a direction that is offset by acceleration. That is, when the liquid amounts of the first liquid and the second liquid are equal, the contact area between the first liquid and the reaction part in each of the first to third reaction steps is the first to third cleaning steps. It is larger than the contact area between the second liquid and the reaction part.

  Therefore, even when the first cleaning liquid 92 is smaller than the sample liquid 91, the first cleaning liquid 92 can contact the entire region of the reaction unit 380 that is in contact with the sample liquid 91. Components other than a single conjugate can be reliably removed. Even when the second cleaning liquid 94 is less than the labeled antibody solution 93, the second cleaning liquid 94 can contact the entire region of the reaction unit 380 that is in contact with the labeled antibody solution 93. Therefore, the second cleaning solution 94 remains in the reaction unit 380. Components other than the two conjugates can be reliably removed. Therefore, more accurate reaction results can be obtained when the substrate solution 95 is reacted with the second conjugate in the third reaction step.

(4) Centrifugal force X2 of each step (S2, S6, S12) in which the liquid is reacted in the reaction unit 380 causes each step (S1, S3, S5, S7, S9, S11) to move the liquid in the inspection chip 2. The centrifugal force is less than X1. Thereby, the energy consumption accompanying execution of the centrifugal treatment can be suppressed, and the liquid can be accurately moved in the inspection chip 2.

(5) The centrifugal force X21 in the first reaction step (S2) is equal to or higher than the centrifugal forces X22, X23 in the second and third reaction steps (S6, S12). Since the first reaction step is executed first among the first to third reaction steps, the amount of the first conjugate produced has a great influence on the final test result. Therefore, the liquid level position of the sample liquid 91 in the reaction part 380 can be accurately controlled by setting the centrifugal force X21 to the centrifugal forces X22 and X23 or more. Thereby, the contact area between the sample liquid 91 and the reaction unit 380 is accurately controlled, and the amount of the first conjugate produced is accurately controlled, so that an accurate test result regarding the liquid reaction can be obtained.

(6) The centrifugal force X31 in the first washing step (S4) is larger than the centrifugal forces X32 and X33 in the second and third washing steps (S8, S10). As a result, the surface tension between the first cleaning liquid 92 and the reaction unit 380 held in the first cleaning process, and between the second cleaning liquid 94 and the reaction unit 380 held in the second and third cleaning processes. In the surface tension, the former is more likely to have a force in the direction offset by acceleration. That is, when the amounts of the first cleaning liquid 92 and the second cleaning liquid 94 are equal, the contact area between the first cleaning liquid 92 and the reaction portion in the first cleaning process is the second cleaning liquid in the second and third cleaning processes. It is larger than the contact area between 94 and the reaction part 380. Even when the amount of the second cleaning liquid 94 is smaller than the amount of the first cleaning liquid 92, the second cleaning liquid 94 can contact the entire region of the reaction unit 380 that is in contact with the first cleaning liquid 92. Therefore, since the wide range of the reaction part 380 can be cleaned while suppressing the amount of the second cleaning liquid 94 that is not involved in the reaction, an accurate test result regarding the liquid reaction can be obtained.

(7) In the fourth liquid feeding step (S7) and the fifth liquid feeding step (S9), the second cleaning liquid 94 is moved downstream from the introduction portion in a plurality of times. The second cleaning step (S8) and the third cleaning step (S10) are performed each time the second cleaning liquid 94 is moved downstream from the introduction unit. In each of the second and third washing steps, the second washing liquid 94 moved downstream from the introduction part is held in the reaction part 380 after the labeled antibody solution 93 has been moved downstream. Of the second and third cleaning steps, the second cleaning step is performed first, and the third cleaning step is performed thereafter. The centrifugal force X33 in the third cleaning step is equal to or higher than the centrifugal force X32 in the second cleaning step.

  According to this, removal of components other than the second conjugate remaining in the reaction unit 380 is performed in a plurality of times by the second and third cleaning steps. Since the acceleration of the second cleaning process is the largest among the second and third cleaning processes, the second cleaning liquid 94 can clean a wide range of the reaction unit 380 in the second cleaning process.

(8) Each of the sample solution 91, the first cleaning solution 92, the labeled antibody solution 93, the second cleaning solution 94, and the substrate solution 95 has a contact angle of 90 degrees or less with respect to the wall surface of the reaction unit 380. Thereby, even when the liquid volume of the second liquid not involved in the reaction is smaller than the liquid volume of the first liquid involved in the reaction, the second liquid is the entire area of the reaction unit 380 that is in contact with the first liquid. Touchable. Therefore, an accurate test result relating to the liquid reaction can be obtained while suppressing the amount of the second liquid that is not involved in the reaction.

<10. Remarks>
The present invention is not limited to the above embodiment, and various modifications can be made. For example, the liquid used in the test chip 2 is not limited to the sample liquid 91, the first cleaning liquid 92, the labeled antibody liquid 93, the second cleaning liquid 94, the substrate solution 95, and the stop liquid 96, and may be other liquids. For example, the liquid involved in the reaction is not limited to the sample solution 91, the labeled antibody solution 93, and the substrate solution 95, and may be a catalyst solution or the like. The liquid not involved in the reaction is not limited to the first cleaning liquid 92 and the second cleaning liquid 94, and may be a diluted liquid or the like.

  The inspection apparatus 1 may revolve the inspection chip 2 around the first axis and rotate the inspection chip 2 around the second axis different from the first axis in the centrifugal process (see FIG. 4). . The angular width at which the test chip 2 is rotated in the centrifugal process is not limited to the rotation angle of 0 degrees to 90 degrees. For example, the inspection apparatus 1 may be rotated at an angular width of 0 to 180 degrees in the centrifugation process. In the centrifugal process, another acceleration may be used instead of the centrifugal force. Other accelerations are exemplified by gravity or the resultant force of gravity and centrifugal force. For example, the inspection apparatus 1 may move or react each liquid by applying gravity or a resultant force of gravity and centrifugal force to the inspection chip 2 in at least one of the steps in the centrifugation process.

  Centrifugal processing can be appropriately changed according to the inspection purpose, inspection method, type of liquid, and the like. For example, in the centrifugation process of the above embodiment (see FIG. 4), the cleaning process for removing components other than the second conjugate remaining in the reaction unit 380 includes the second cleaning process (S8) and the third cleaning process (S10). As a result, two times are executed. Instead, the cleaning process for removing components other than the second conjugate remaining in the reaction unit 380 may be performed only once, or may be performed three or more times. Similarly, the cleaning process for removing components other than the first conjugate remaining in the reaction unit 380 is not limited to a single first cleaning process (S4), and may be performed a plurality of times.

  In the embodiment and the modification, the inspection chip 2 is an example of the “inspection chip” in the present invention. Centrifugal force is an example of “acceleration” in the present invention. Centrifugation (see FIG. 4) is an example of the “inspection method” of the present invention. Each of the sample solution 91, the labeled antibody solution 93, and the substrate solution 95 is an example of the “first solution” in the present invention. Each of the first cleaning liquid 92 and the second cleaning liquid 94 is an example of the “second liquid” in the present invention. The sample solution introduction unit 310, the first washing solution introduction unit 320, the labeled antibody solution introduction unit 330, the second washing solution introduction unit 340, the substrate solution introduction unit 350, and the stop solution introduction unit 360 are examples of the “introduction unit” of the present invention. It is. The reaction unit 380 is an example of the “holding unit” and “reaction unit” in the present invention. The first liquid feeding step (S1) is an example of the “first moving step” in the present invention. The first reaction step (S2) is an example of the “first holding step” in the present invention. The second liquid feeding step (S3) is an example of the “second moving step” in the present invention. The first cleaning step (S4) is an example of the “second holding step” in the present invention.

  The third liquid feeding step (S5) is an example of the “third moving step” in the present invention. The second reaction step (S6) is an example of the “third holding step” in the present invention. The fourth liquid feeding step (S7) and the fifth liquid feeding step (S9) are examples of the “fourth moving step” and the “plurality of cleaning liquid moving steps” in the present invention. The second cleaning step (S8) and the third cleaning step (S10) are examples of the “fourth holding step” and the “plurality of cleaning liquid holding steps” in the present invention. The sixth liquid feeding step (S11) is an example of the “fifth moving step” in the present invention. The third reaction step (S12) is an example of the “fifth holding step” in the present invention. The second cleaning step (S8) is an example of the “first cleaning step” in the present invention. The third cleaning step (S10) is an example of “at least one subsequent cleaning step” in the present invention.

  The inspection system 3 is an example of the “inspection system” in the present invention. The inspection apparatus 1 is an example of the “inspection apparatus” in the present invention. The CPU 101 that executes S1 is an example of the “first moving unit” in the present invention. The CPU 101 that executes S2 is an example of the “first holding unit” in the present invention. The CPU 101 that executes S3 is an example of the “second moving means” in the present invention. The CPU 101 that executes S4 is an example of the “second holding unit” in the present invention.

DESCRIPTION OF SYMBOLS 1 Inspection apparatus 2 Inspection chip 3 Inspection system 91 Sample liquid 92 1st washing | cleaning liquid 93 Labeled antibody liquid 94 2nd washing | cleaning liquid 95 Substrate solution 101 CPU
310 Sample solution introduction unit 320 First washing solution introduction unit 330 Labeled antibody solution introduction unit 340 Second washing solution introduction unit 350 Substrate solution introduction unit 360 Stop solution introduction unit 380 Reaction unit

Claims (10)

An inspection method for inspecting by applying acceleration to an inspection chip,
The inspection chip is
An introduction part that is a region where a first liquid that is a liquid involved in the reaction and a second liquid that is a liquid not involved in the reaction are introduced;
A holding portion that is connected to the downstream side of the introduction portion and is a region capable of holding the first liquid and the second liquid flowing out from the introduction portion;
The inspection method is:
A first moving step of moving the first liquid downstream from the introduction part by applying acceleration to the inspection chip;
A first holding step of holding the first liquid in the holding unit by applying acceleration to the inspection chip after the execution of the first moving step;
After execution of the first holding step, the first liquid is moved downstream from the holding unit and the second liquid is moved downstream from the introducing unit by applying an acceleration to the inspection chip. A second transfer step;
A second holding step for holding the second liquid in the holding portion by applying acceleration to the inspection chip after the second moving step is performed;
The inspection method, wherein the acceleration applied to the inspection chip in the first holding step is greater than the acceleration applied to the inspection chip in the second holding step. The holding part includes a reaction part in which an immobilized antibody is arranged,
The first liquid is a liquid that reacts with the immobilized antibody in the reaction part,
The second liquid is a cleaning liquid for cleaning the reaction part,
In the first holding step, the first liquid is allowed to react with the immobilized antibody by holding the first liquid in the reaction part,
The inspection method according to claim 1, wherein in the second holding step, the reaction part is washed with the second liquid by holding the second liquid in the reaction part. The first solution includes a sample solution containing a substance to be examined, a labeled antibody solution containing an enzyme-labeled antibody, and a substrate solution that reacts with the enzyme-labeled antibody.
The second liquid includes a first cleaning liquid and a second cleaning liquid as the cleaning liquid,
In the first moving step, the sample liquid is moved downstream from the introduction part,
In the first holding step, the sample solution is held in the reaction unit, thereby binding the test target substance to the immobilized antibody to generate a first conjugate,
In the second moving step, the first cleaning liquid is moved downstream from the introduction part,
The second holding step removes components other than the first conjugate remaining in the reaction part by holding the first cleaning liquid in the reaction part,
Further, the inspection method includes:
After execution of the second holding step, acceleration is applied to the test chip to move the first cleaning liquid from the reaction part to the downstream side and to move the labeled antibody liquid from the introduction part to the downstream side. A third transfer step;
After the execution of the third moving step, by causing acceleration to act on the test chip, the labeled antibody solution is held in the reaction part, and the enzyme-labeled antibody is specifically bound to the first conjugate. A third holding step to produce a second conjugate;
After execution of the third holding step, acceleration is applied to the test chip to move the labeled antibody solution from the reaction unit to the downstream side, and to move the second cleaning solution from the introduction unit to the downstream side. A fourth moving step;
After execution of the fourth moving step, by applying acceleration to the inspection chip, the second cleaning liquid is held in the reaction unit, and components other than the second conjugate remaining in the reaction unit are removed. A fourth holding step;
After the execution of the fourth holding step, the second cleaning liquid is moved downstream from the reaction unit and the substrate solution is moved downstream from the introduction unit by applying acceleration to the inspection chip. Five moving steps;
After the execution of the fifth movement step, by causing acceleration to act on the inspection chip, the reaction unit holds the substrate solution, and the fifth holding step causes the substrate solution to react with the second conjugate, With
The acceleration applied to the inspection chip in each of the first holding process, the third holding process, and the fifth holding process acts on the inspection chip in each of the second holding process and the fourth holding process. The inspection method according to claim 2, wherein the inspection method is greater than a measured acceleration.   The acceleration applied to the inspection chip in each of the first holding step, the third holding step, and the fifth holding step is the same as that of the first moving step, the third moving step, and the fifth moving step. The inspection method according to claim 3, wherein each of the accelerations is equal to or less than an acceleration applied to the inspection chip.   The acceleration applied to the inspection chip in the first holding step is greater than or equal to the acceleration applied to the inspection chip in each of the third holding step and the fifth holding step. 4. The inspection method according to 4.   6. The inspection method according to claim 3, wherein an acceleration applied to the inspection chip in the second holding step is larger than an acceleration applied to the inspection chip in the fourth holding step. . The fourth moving step includes a plurality of cleaning liquid moving steps for dividing the second cleaning liquid into a plurality of times and moving the second cleaning liquid downstream from the introduction unit,
In the fourth holding step, each time each of the plurality of washing solution moving steps is executed, the second washing solution moved downstream from the introduction unit is moved after the labeled antibody solution is moved downstream. A plurality of cleaning liquid holding steps to be held in the reaction part of,
The plurality of cleaning liquid discharging steps include an initial cleaning step that is first executed among the plurality of cleaning liquid discharging steps, and at least one subsequent cleaning step that is executed after the initial cleaning step,
The acceleration applied to the inspection chip in each of the at least one subsequent cleaning step is equal to or higher than the acceleration applied to the inspection chip in the initial cleaning step. Inspection method described.   The inspection method according to claim 1, wherein each of the first liquid and the second liquid has a contact angle of 90 degrees or less with respect to a wall surface of the holding portion.   9. The inspection method according to claim 1, wherein the acceleration applied to the inspection chip is a centrifugal force. An inspection system including an inspection chip in which a liquid can move and an inspection device that applies acceleration to the inspection chip,
The inspection chip is
An introduction part that is a region where a first liquid that is a liquid involved in the reaction and a second liquid that is a liquid not involved in the reaction are introduced;
A holding portion that is connected to the downstream side of the introduction portion and is a region capable of holding the first liquid and the second liquid flowing out from the introduction portion;
The inspection device includes:
A first moving means for performing a first moving step of moving the first liquid downstream from the introduction portion by applying an acceleration to the inspection chip;
A first holding means for performing a first holding step of holding the first liquid in the holding unit by applying acceleration to the inspection chip after the execution of the first moving step;
After execution of the first holding step, the first liquid is moved downstream from the holding unit and the second liquid is moved downstream from the introducing unit by applying an acceleration to the inspection chip. Second moving means for performing a second moving step;
A second holding means for performing a second holding step for holding the second liquid in the holding unit by applying an acceleration to the inspection chip after the second moving step is performed;
The inspection system, wherein an acceleration applied to the inspection chip in the first holding step is larger than an acceleration applied to the inspection chip in the second holding step.

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